Harnish et al., U.S. Pat. No. 4,841,052 issued Jun. 20, 1989 discloses bis-naphthalic acid imides useful as charge-regulating substances in electrophotographic toners.
Brana et al., U.S. Pat. No. 4,874,883 issued Oct. 17, 1989 discloses anticancer compounds of the formula: ##STR2## wherein X, X', X" and X'" are identical or different and are each H, NO.sub.2, NH.sub.2, C.sub.1 -C.sub.6 alkylamino, di-C.sub.1 -C.sub.6 alkylamino, OH, C.sub.1 -C.sub.6 alkoxy, halogen, trihalomethyl, C.sub.1 -C.sub.6 alkyl, formyl, C.sub.1 -C.sub.6 alkylcarbonyl, ureyl, C.sub.1 -C.sub.6 alkylureyl and R is a straight chain or branched C.sub.4 -C.sub.10 alkylene which is interrupted at one or two points in the chain by a secondary or tertiary amino group, where 2 nitrogen atoms may additionally be bonded to one another by an alkylene group, or a salt with a physiologically tolerated acid.
Ardecky et al., U.S. Pat. No. 5,086,059, issued Feb. 4, 1992 discloses naphthalimides containing an ethano bridge across the 4 and 5 positions of the naphthalimide ring. Those compounds were said to be efficacious against cancer and more soluble in aqueous media than prior art compounds.
Sun, U.S. Pat. No. 5,206,249, issued Apr. 27, 1993, discloses bisnaphthalimides with naphthalimide rings containing at least one nitro substituent, joined by branched bridging moieties as anticancer drugs. Sun et al, PCT/US92/10525, published Jun. 24, 1993 discloses bis-naphthalimides with naphthalimide rings containing at least one nitro substituent, joined by branched bridging moieties.
Brana et al. 1992 Germ. Pat. Appln. 42 32 739.3 Sept. 30, 1992, discloses asymmetric bis-naphthalimides.
Harnish, U.S. Pat. No. 4,919,848, discloses bisnaphthalimides which are intermediates for the preparation of compounds for quenching the fluorescence generated by anionic optical brighteners.
Heretofore it had been thought that substitution, particularly nitro substitution, on the naphthalimide ring(s) is important for anti-tumor efficacy of bis-naphthalimides, whether via interactions involved in DNA intercalation of the nitrobisnapthalimide or otherwise. We have surprisingly found, however, that such nitro substitution is not required for anti-tumor activity after all, and in fact, that certain bisnaphthalimides which lack nitro substitution and/or which have new combinations of ring substituents and bridge geometry, as described in detail below, provide anti-tumor compositions with improved toxicity profiles, anti-tumor selectivity and/or solubility.